Recent work from this laboratory has shown that in the spinal cat, the information transmitted from Ia fibers to motoneurons can be modulated by changing the degree of correlated activity of the interneurons impinging presynaptically onto the Ia-motoneuron monosynaptic pathway. Descending fibers (in the ventromedial fasciculus) making monosynaptic contacts with spinal motoneurons do not appear to be subjected to this presynaptic control. As a consequence, conditioning volleys to sensory nerves may affect in differential manner the information conveyed by particular sets of motoneurons depending on which pathways are utilized to activate these cells. The investigations described in this application are aimed to analyze if this differential mechanism of presynaptic modulation operates in other pathways besides the Ia motoneuron pathway, particularly on interneurons at the intermediate nucleus receiving monosynaptic convergent input from afferent fibers and descending supraspinal fibers. Experiments have been also planned to test the effects of natural stimulation of cutaneous and muscle afferents on the correlated fluctuations of transmitter released by afferent and descending fibers. It is expected that this approach will provide information on the mechanisms, specificity, and functional significance of the presynaptic modulation of transmitter release. An additional objective of these investigations is to initiate a comparative study of the mechanisms involved in the presynaptic control of transmitter release in lower vertebrates, particularly in the grog and fishes. It is expected that this knowledge will contribute significantly to our understanding of the hierachy of the presynaptic mechanisms controlling information transmission.